title: Characterization of SHP-1 protein tyrosine phosphatase transcripts, protein isoforms and phosphatase activity in epithelial cancer cells.
abstract: We identified 7 SHP-1 (PTPN6) transcripts using epithelial cancer-derived cell lines. Four were shown to utilize the epithelial promoter 1 to transcribe a full-length, a partial (exon 3) or complete (exons 3 & 4) deletion of the N-SH2 domain, and also a non-coding transcript having a stop codon caused by a frame shift due to intron 2 retention. Three additional transcripts were shown to utilize the hematopoietic promoter 2 to transcribe a full-length, a partial (exon 3) deletion of the N-SH2 domain and a non-coding transcript with intron 2 retention. We show that endogenous proteins corresponding to the open-reading-frame (ORF) transcripts are produced. Using GST-fusion proteins we show that each product of the ORF SHP-1 transcripts has phosphatase activity and isoforms with an N-SH2 deletion have increased phosphatase activity and novel protein-protein interactions. This study is the first to document utilization of promoter 2 by SHP-1 transcripts and a noncoding transcript in human epithelial cells.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2M1, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M1, Canada.
authors.forename: Sevan
authors.initials: S
authors.lastname: Evren
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON M5G 2M1, Canada; Canadian Blood Services, Research and Development, Toronto, ON M5G 2M1, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 2M1, Canada.
authors.forename: Simmy
authors.initials: S
authors.lastname: Wan
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2M1, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M1, Canada; Canadian Blood Services, Research and Development, Toronto, ON M5G 2M1, Canada.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Ma
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON M5G 2M1, Canada.
authors.forename: Soad
authors.initials: S
authors.lastname: Fahim
authors.affiliation: Toronto General Research Institute, Division of Molecular Therapeutics, Toronto, ON M5G 2M1, Canada.
authors.forename: Nayha
authors.initials: N
authors.lastname: Mody
authors.affiliation: Toronto General Research Institute, Division of Molecular Therapeutics, Toronto, ON M5G 2M1, Canada.
authors.forename: Darinka
authors.initials: D
authors.lastname: Sakac
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2M1, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 2M1, Canada; Toronto General Research Institute, Division of Molecular Therapeutics, Toronto, ON M5G 2M1, Canada.
authors.forename: Tianru
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2M1, Canada; Department of Medicine, University of Toronto, Toronto, ON M5G 2M1, Canada; Canadian Blood Services, Research and Development, Toronto, ON M5G 2M1, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 2M1, Canada; Toronto General Research Institute, Division of Molecular Therapeutics, Toronto, ON M5G 2M1, Canada.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
mesh_terms: D017398:Alternative Splicing; D045744:Cell Line, Tumor; D005091:Exons; D016368:Frameshift Mutation; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D061986:MCF-7 Cells; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D022661:RNA, Untranslated; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: Alternatively spliced transcripts; SHP-1; SHP-1 protein isoforms; Tyrosine phosphatase; mRNA